Neurologic involvment is one of the most serious and common complications of Lyme disease (LD). Yet there is no reliable test available to detect this at an early stage. LD cases due to Borrelia burgdorferi (Bb) are increasing. Serious consequences can occur when Bb invades the central nervous system(CNS). Early detection of invasion would permit CNS-penetrating antibiotics to reduce sequelae. Our objective is to develop an assay to detect active CNS infection. Preliminary data suggests that Bb immune complexes (IC) analysis in cerebrospinal fluid (CSF) is a potential test. Specific Aim : To determine whether early neurologic LD patients have CSF IC which contain anti-Bb antibodies (Abs) and Bb antigens (Ags). Hypothesis: Early neurologic LD patients form IC in CSF. Rationale: In many infections IC Ab is found bound to its Ag target earlier than free Ab. In contrast to free Ab, specific IC Ab or Ag reflects active infection. Samples are already banked from neurologic LD patients with both erythema migrans AND microbiological confirmation. We will study blinded CSF specimens and compare CSF BbIC to free Bb Ab assays, PCR, and cultures (data already available). BbIC will be isolated by a proven simple technique, polyethylene glycol. BbIC Ab and Ag will be identified. Focus will be towards on specific and in vivo expressed Bb Ags. Results will be statistically analyzed. Phase 2 will be designed for broadscale usage and refinement.